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  • Oxford University Press (OUP)  (92)
  • 1
    Online Resource
    Online Resource
    Modelling of plant circadian clock for characterizing hypocotyl growth under different light quality conditions
    Oxford University Press (OUP) ; 2022
    In:  in silico Plants Vol. 4, No. 1 ( 2022-01-01)
    Details
    In: in silico Plants, Oxford University Press (OUP), Vol. 4, No. 1 ( 2022-01-01)
    Abstract: To meet the ever-increasing global food demand, the food production rate needs to be increased significantly in the near future. Speed breeding is considered as a promising agricultural technology solution to achieve the zero-hunger vision as specified in the United Nations Sustainable Development Goal 2. In speed breeding, the photoperiod of the artificial light has been manipulated to enhance crop productivity. In particular, regulating the photoperiod of different light qualities rather than solely white light can further improve speed breading. However, identifying the optimal light quality and the associated photoperiod simultaneously remains a challenging open problem due to complex interactions between multiple photoreceptors and proteins controlling plant growth. To tackle this, we develop a first comprehensive model describing the profound effect of multiple light qualities with different photoperiods on plant growth (i.e. hypocotyl growth). The model predicts that hypocotyls elongated more under red light compared to both red and blue light. Drawing similar findings from previous related studies, we propose that this might result from the competitive binding of red and blue light receptors, primarily Phytochrome B (phyB) and Cryptochrome 1 (cry1) for the core photomorphogenic regulator, CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1). This prediction is validated through an experimental study on Arabidopsis thaliana. Our work proposes a potential molecular mechanism underlying plant growth under different light qualities and ultimately suggests an optimal breeding protocol that takes into account light quality.
    Type of Medium: Online Resource
    ISSN: 2517-5025
    URL: Article
    DOI: 10.1093/insilicoplants/diac001
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 3019806-9
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  • 2
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    Hierarchical Bayesian models of transcriptional and translational regulation processes with delays
    Oxford University Press (OUP) ; 2021
    In:  Bioinformatics Vol. 38, No. 1 ( 2021-12-22), p. 187-195
    Details
    In: Bioinformatics, Oxford University Press (OUP), Vol. 38, No. 1 ( 2021-12-22), p. 187-195
    Abstract: Simultaneous recordings of gene network dynamics across large populations have revealed that cell characteristics vary considerably even in clonal lines. Inferring the variability of parameters that determine gene dynamics is key to understanding cellular behavior. However, this is complicated by the fact that the outcomes and effects of many reactions are not observable directly. Unobserved reactions can be replaced with time delays to reduce model dimensionality and simplify inference. However, the resulting models are non-Markovian, and require the development of new inference techniques. Results We propose a non-Markovian, hierarchical Bayesian inference framework for quantifying the variability of cellular processes within and across cells in a population. We illustrate our approach using a delayed birth–death process. In general, a distributed delay model, rather than a popular fixed delay model, is needed for inference, even if only mean reaction delays are of interest. Using in silico and experimental data we show that the proposed hierarchical framework is robust and leads to improved estimates compared to its non-hierarchical counterpart. We apply our method to data obtained using time-lapse microscopy and infer the parameters that describe the dynamics of protein production at the single cell and population level. The mean delays in protein production are larger than previously reported, have a coefficient of variation of around 0.2 across the population, and are not strongly correlated with protein production or growth rates. Availability and implementation Accompanying code in Python is available at https://github.com/mvcortez/Bayesian-Inference. Contact kresimir.josic@gmail.com or jaekkim@kaist.ac.kr or cbskust@korea.ac.kr Supplementary information Supplementary data are available at Bioinformatics online.
    Type of Medium: Online Resource
    ISSN: 1367-4803 , 1367-4811
    URL: Article
    DOI: 10.1093/bioinformatics/btab618
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1468345-3
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  • 3
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    Bayesian inference of distributed time delay in transcriptional and translational regulation
    Oxford University Press (OUP) ; 2020
    In:  Bioinformatics Vol. 36, No. 2 ( 2020-01-15), p. 586-593
    Details
    In: Bioinformatics, Oxford University Press (OUP), Vol. 36, No. 2 ( 2020-01-15), p. 586-593
    Abstract: Advances in experimental and imaging techniques have allowed for unprecedented insights into the dynamical processes within individual cells. However, many facets of intracellular dynamics remain hidden, or can be measured only indirectly. This makes it challenging to reconstruct the regulatory networks that govern the biochemical processes underlying various cell functions. Current estimation techniques for inferring reaction rates frequently rely on marginalization over unobserved processes and states. Even in simple systems this approach can be computationally challenging, and can lead to large uncertainties and lack of robustness in parameter estimates. Therefore we will require alternative approaches to efficiently uncover the interactions in complex biochemical networks. Results We propose a Bayesian inference framework based on replacing uninteresting or unobserved reactions with time delays. Although the resulting models are non-Markovian, recent results on stochastic systems with random delays allow us to rigorously obtain expressions for the likelihoods of model parameters. In turn, this allows us to extend MCMC methods to efficiently estimate reaction rates, and delay distribution parameters, from single-cell assays. We illustrate the advantages, and potential pitfalls, of the approach using a birth–death model with both synthetic and experimental data, and show that we can robustly infer model parameters using a relatively small number of measurements. We demonstrate how to do so even when only the relative molecule count within the cell is measured, as in the case of fluorescence microscopy. Availability and implementation Accompanying code in R is available at https://github.com/cbskust/DDE_BD. Supplementary information Supplementary data are available at Bioinformatics online.
    Type of Medium: Online Resource
    ISSN: 1367-4803 , 1367-4811
    URL: Article
    DOI: 10.1093/bioinformatics/btz574
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1468345-3
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  • 4
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    Efficacy and safety of switching from reference adalimumab to CT-P17 (100 mg/ml): 52-week randomized, double-blind study in rheumatoid arthritis
    Oxford University Press (OUP) ; 2022
    In:  Rheumatology Vol. 61, No. 4 ( 2022-04-11), p. 1385-1395
    Details
    In: Rheumatology, Oxford University Press (OUP), Vol. 61, No. 4 ( 2022-04-11), p. 1385-1395
    Abstract: To compare the safety and efficacy of switching from reference adalimumab to adalimumab biosimilar CT-P17 with continuing reference adalimumab/CT-P17 in active RA. Methods This double-blind, phase III study randomized (1:1) subjects with active RA to receive 40 mg (100 mg/ml) CT-P17 or European Union-sourced reference adalimumab subcutaneously every 2 weeks (Q2W) until week (W) 24 [treatment period (TP) 1]. Thereafter, subjects receiving reference adalimumab were randomized (1:1) to continue reference adalimumab or switch to CT-P17 from W26 (both Q2W until W48; TP2). Subjects receiving CT-P17 in TP1 continued CT-P17. W0–W24 results were previously reported; we present W26–W52 findings. End points were efficacy (including joint damage progression), pharmacokinetics, safety and immunogenicity. Results Of 607 subjects who initiated TP2 treatment, 303 continued CT-P17, 153 continued reference adalimumab and 151 switched to CT-P17. Efficacy improvements up to W24 were maintained during TP2; efficacy was comparable among groups. At W52, 20% improvement in ACR response rates were 80.5% (continued CT-P17), 77.8% (continued reference adalimumab) and 82.2% (switched to CT-P17). Joint damage progression was minimal. Mean trough serum adalimumab concentrations were similar among groups. CT-P17 and reference adalimumab safety profiles were numerically similar and switching did not affect immunogenicity. At W52, 28.4% (continued CT-P17), 27.0% (continued reference adalimumab) and 28.3% (switched to CT-P17) of subjects were anti-drug antibody-positive. Conclusion Efficacy, pharmacokinetics, safety and immunogenicity of CT-P17 and reference adalimumab were comparable after 1 year of treatment, including after switching from reference adalimumab to CT-P17. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT03789292.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    URL: Article
    DOI: 10.1093/rheumatology/keab460
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1474143-X
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  • 5
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    A real-time, personalized sleep intervention using mathematical modeling and wearable devices
    Oxford University Press (OUP) ; 2023
    In:  SLEEP Vol. 46, No. 9 ( 2023-09-08)
    Details
    In: SLEEP, Oxford University Press (OUP), Vol. 46, No. 9 ( 2023-09-08)
    Abstract: The prevalence of artificial light exposure has enabled us to be active any time of the day or night, leading to the need for high alertness outside of traditional daytime hours. To address this need, we developed a personalized sleep intervention framework that analyzes real-world sleep–wake patterns obtained from wearable devices to maximize alertness during specific target periods. Our framework utilizes a mathematical model that tracks the dynamic sleep pressure and circadian rhythm based on the user’s sleep history. In this way, the model accurately predicts real-time alertness, even for shift workers with complex sleep and work schedules (N = 71, t = 13~21 days). This allowed us to discover a new sleep–wake pattern called the adaptive circadian split sleep, which incorporates a main sleep period and a late nap to enable high alertness during both work and non-work periods of shift workers. We further developed a mobile application that integrates this framework to recommend practical, personalized sleep schedules for individual users to maximize their alertness during a targeted activity time based on their desired sleep onset and available sleep duration. This can reduce the risk of errors for those who require high alertness during nontraditional activity times and improve the health and quality of life for those leading shift work-like lifestyles.
    Type of Medium: Online Resource
    ISSN: 0161-8105 , 1550-9109
    URL: Article
    DOI: 10.1093/sleep/zsad179
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2056761-3
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  • 6
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    Inferring causality in biological oscillators
    Oxford University Press (OUP) ; 2021
    In:  Bioinformatics Vol. 38, No. 1 ( 2021-12-22), p. 196-203
    Details
    In: Bioinformatics, Oxford University Press (OUP), Vol. 38, No. 1 ( 2021-12-22), p. 196-203
    Abstract: Fundamental to biological study is identifying regulatory interactions. The recent surge in time-series data collection in biology provides a unique opportunity to infer regulations computationally. However, when components oscillate, model-free inference methods, while easily implemented, struggle to distinguish periodic synchrony and causality. Alternatively, model-based methods test the reproducibility of time series given a specific model but require inefficient simulations and have limited applicability. Results We develop an inference method based on a general model of molecular, neuronal and ecological oscillatory systems that merges the advantages of both model-based and model-free methods, namely accuracy, broad applicability and usability. Our method successfully infers the positive and negative regulations within various oscillatory networks, e.g. the repressilator and a network of cofactors at the pS2 promoter, outperforming popular inference methods. Availability and implementation We provide a computational package, ION (Inferring Oscillatory Networks), that users can easily apply to noisy, oscillatory time series to uncover the mechanisms by which diverse systems generate oscillations. Accompanying MATLAB code under a BSD-style license and examples are available at https://github.com/Mathbiomed/ION. Additionally, the code is available under a CC-BY 4.0 License at https://doi.org/10.6084/m9.figshare.16431408.v1. Supplementary information Supplementary data are available at Bioinformatics online.
    Type of Medium: Online Resource
    ISSN: 1367-4803 , 1367-4811
    URL: Article
    DOI: 10.1093/bioinformatics/btab623
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1468345-3
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  • 7
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    Bifidobacterium lactis inhibits NF-κB in intestinal epithelial cells and prevents acute colitis and colitis-associated colon cancer in mice
    Oxford University Press (OUP) ; 2010
    In:  Inflammatory Bowel Diseases Vol. 16, No. 9 ( 2010-09), p. 1514-1525
    Details
    In: Inflammatory Bowel Diseases, Oxford University Press (OUP), Vol. 16, No. 9 ( 2010-09), p. 1514-1525
    Type of Medium: Online Resource
    ISSN: 1078-0998
    URL: Article
    DOI: 10.1002/ibd.21262
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2010
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  • 8
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    Mycobacterial Characteristics and Treatment Outcomes in Mycobacterium abscessus Lung Disease
    Oxford University Press (OUP) ; 2017
    In:  Clinical Infectious Diseases Vol. 64, No. 3 ( 2017-02-01), p. 309-316
    Details
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 64, No. 3 ( 2017-02-01), p. 309-316
    Abstract: Treatment outcomes of patients with Mycobacterium abscessus subspecies abscessus lung disease are poor, and the microbial characteristics associated with treatment outcomes have not been studied systematically. The purpose of this study was to identify associations between microbial characteristics and treatment outcomes in patients with M. abscessus lung disease. Methods Sixty-seven consecutive patients with M. abscessus lung disease undergoing antibiotic treatment for ≥12 months between January 2002 and December 2012 were included. Morphotypic and genetic analyses were performed on isolates from 44 patients. Results Final sputum conversion to culture negative occurred in 34 (51%) patients. Compared to isolates from 24 patients with persistently positive cultures, pretreatment isolates from 20 patients with final negative conversion were more likely to exhibit smooth colonies (9/20, 45% vs 2/24, 8%; P = .020), susceptibility to clarithromycin (7/20, 35% vs 1/24, 4%; P = .015), and be of the C28 sequevar with regard to the erm(41) gene (6/20, 30% vs 1/24, 4%; P = .035). Mycobacterium abscessus lung disease recurred in 5 (15%) patients after successful completion of antibiotic therapy. Genotypic analysis revealed that most episodes (22/24, 92%) of persistently positive cultures during antibiotic treatment and all cases of microbiologic recurrence after treatment completion were caused by different M. abscessus genotypes within a patient. Conclusions Precise identification to the subspecies level and analysis of mycobacterial characteristics could help predict treatment outcomes in patients with M. abscessus lung disease. Treatment failures and recurrences are frequently associated with multiple genotypes, suggesting reinfection. Clinical Trials Registration NCT00970801.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    URL: Article
    DOI: 10.1093/cid/ciw724
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2017
    detail.hit.zdb_id: 2002229-3
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  • 9
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    Immune Response Kinetics Following a Third Heterologous BNT162b2 Booster Dose After Primary 2-Dose ChAdOx1 Vaccination in Relation to Omicron Breakthrough Infection: A Prospective Nationwide Cohort Study in South Korea
    Oxford University Press (OUP) ; 2023
    In:  Open Forum Infectious Diseases Vol. 10, No. 7 ( 2023-07-01)
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 10, No. 7 ( 2023-07-01)
    Abstract: Immune responses to each vaccine must be investigated to establish effective vaccination strategies for the ongoing coronavirus disease (COVID-19) pandemic. We investigated the long-term kinetics of immune responses after heterologous booster vaccination in relation to Omicron breakthrough infection (BI). Methods Our study included 373 healthcare workers who received primary ChAdOx1 vaccine doses and a third BNT162b2 vaccine dose. BIs that occurred after the third vaccine were investigated. Blood specimens were collected before and 3 months after the booster dose from participants without BI and 1, 4, and 6 months after BI from participants who experienced BI. Spike-specific binding and neutralizing antibody levels against the wild-type virus, Omicron BA.1, and Omicron BA.5, as well as cellular responses, were analyzed. Results A total of 346 participants (82 in the no BI group; 192 in the BI group during the BA.1/BA.2 period; 72 in the BI group during the BA.5 period) were included in the analysis. Participants without BI exhibited the highest binding and neutralizing antibody concentrations and greatest cellular response 1 month after the third vaccination, which reached a nadir by the ninth month. Antibody and cellular responses in participants who experienced BI substantially increased postinfection. Neutralizing antibody titers in individuals who experienced BI during the BA.1/BA.2 period showed more robust increase against wild-type virus than against BA.1 and BA.5. Conclusions Our findings provide evidence of antigenic imprinting in participants who received a heterologous booster vaccination, thereby serving as a foundation for further studies on the impact of BIs on immune responses.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofad363
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2757767-3
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  • 10
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    Induction of Thioredoxin Is Required for Nodule Development to Reduce Reactive Oxygen Species Levels in Soybean Roots
    Oxford University Press (OUP) ; 2005
    In:  Plant Physiology Vol. 139, No. 4 ( 2005-12-01), p. 1881-1889
    Details
    In: Plant Physiology, Oxford University Press (OUP), Vol. 139, No. 4 ( 2005-12-01), p. 1881-1889
    Abstract: Nodules are formed on legume roots as a result of signaling between symbiotic partners and in response to the activities of numerous genes. We cloned fragments of differentially expressed genes in spot-inoculated soybean (Glycine max) roots. Many of the induced clones were similar to known genes related to oxidative stress, such as thioredoxin and β-carotene hydroxylase. The deduced amino acid sequences of full-length soybean cDNAs for thioredoxin and β-carotene hydroxylase were similar to those in other species. In situ RNA hybridization revealed that the thioredoxin gene is expressed on the pericycle of 2-d-old nodules and in the infected cells of mature nodules, suggesting that thioredoxin is involved in nodule development. The thioredoxin promoter was found to contain a sequence resembling an antioxidant responsive element. When a thioredoxin mutant of yeast was transformed with the soybean thioredoxin gene it became hydrogen peroxide tolerant. These observations prompted us to measure reactive oxygen species levels. These were decreased by 3- to 5-fold in 7-d-old and 27-d-old nodules, coincident with increases in the expression of thioredoxin and β-carotene hydroxylase genes. Hydrogen peroxide-producing regions identified with cerium chloride were found in uninoculated roots and 2-d-old nodules, but not in 7-d-old and 27-d-old nodules. RNA interference-mediated repression of the thioredoxin gene severely impaired nodule development. These data indicate that antioxidants such as thioredoxin are essential to lower reactive oxygen species levels during nodule development.
    Type of Medium: Online Resource
    ISSN: 1532-2548 , 0032-0889
    URL: Article
    DOI: 10.1104/pp.105.067884
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2005
    detail.hit.zdb_id: 2004346-6
    detail.hit.zdb_id: 208914-2
    SSG: 12
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